Depression is a major cause of disease-related disability and confers substantial consequences to physical and psychological health. Longitudinal research indicates that depression increases dramatically in adolescence, particularly for girls. The present study will draw upon data from the Wisconsin Study of Families and Work (WSFW), a longitudinal study of 400 children and their families, to test genetic and temperament models of the development of depression and emergence of a gender difference in depression. Models will be analyzed using statistical techniques appropriate for longitudinal data sets, including latent growth curve models. Specific aims are: 1) Examine whether the short allele of 5-HTTLPR and the three-repeat allele of MAOA- uVNTR, in interaction with negative life events, predict more depressive symptoms and disorders in adolescence;2) Examine whether higher negative affectivity, in interaction with negative life events, predicts more depressive symptoms and disorders in adolescence;3) Examine whether the effects of genetic variation on depression are mediated by negative affectivity, which in turn interacts with negative life events to predict depression;and 4) Evaluate possible explanations for the emergence of a gender difference in depression: a) in the case of MAOA-uVNTR, which is X-linked, girls may have greater genetic vulnerability to depression if the risk allele is dominant or co-dominant;b) there exist gender differences in temperament that result in more girls than boys having a temperament that confers vulnerability to depression;c) beginning in adolescence, girls experience more negative life events than do boys;or d) complex gender differences indicated by significant gender interactions signal different pathways to depression for girls and boys. Corresponding to NIH concerns to understand the causes of mental disorders, this research will aid understandings of the development of depression, and in particular the emergence of a gender difference in depression, to inform and improve prevention and treatment of depression. PUBLIC HEALTH RELEVANCE: The goal of this research is to better understand the processes through which depression develops in adolescence, and in particular, the reasons why females are more likely than males to experience depression. This knowledge will aid researchers and clinicians in their development of prevention efforts and treatment plans